Biochemical mechanisms underlying enzyme development in differentiating tissues are under investigation, the postnatal development and hormonal control of rat liver and epidermal serving as a model system. Although liver mass is reduced, hepatic histidase biosynthesis, relative to total soluble protein synthesis, and catalytic activity is markedly increased following hypophysectomy. Thus the pituitary secretes factor(s) which suppress liver histidase synthesis. Although prolactin does not alter histidase biosynthesis in hypophysectomized rats, triiodothyronine is a potent suppressor of the synthesis of the enzyme and may be the principle mediator in pituitary suppression of de novo hepatic histidase synthesis. The mechanisms underlying refractoriness of liver histidase to hormonal inducers at certain developmental stages have been explored. Whereas glucagon induced elevations in de novo histidase synthesis is maintained throughout postnatal life, glucocorticoidal stimulation of enzyme synthesis is evident in immature animals, but wanes at adulthood. These results imply no significant developmental alterations during this period in hepatic glucocorticoid receptors, (since other enzymes are inducible by this hormone), nor in histidase degradative rates. These data rather suggest that developmental modifications may occur at the level of receptor interaction with specific nuclear acceptor sites, transcription, transcript processing and/or translation.